Identifying resistance to CDK4/6 inhibitors in breast cancer

Identification and Monitoring of Resistance to First-line Treatment with CDK 4/6 Inhibitors in Combination with Aromatase Inhibitors in Patients with Metastatic Luminal Breast Cancer Through Non-invasive Biomarkers

This study is trying to find out why some women with a specific type of advanced breast cancer don't respond to a common treatment that includes a CDK4/6 inhibitor and an aromatase inhibitor by collecting and analyzing their blood and tissue samples during treatment.

Quick facts

• Study type: Observational
• Enrollment: 150 (estimated)
• Sex: Female
• Sponsor: Fondazione Sandro Pitigliani (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Prato, Tuscany)
• Trial ID: NCT04660435 on ClinicalTrials.gov

What this trial studies

This observational study aims to collect biological samples from women with ER-positive and HER2-negative metastatic breast cancer who are candidates for first-line treatment with an aromatase inhibitor and a CDK4/6 inhibitor. Patients will receive standard treatment while blood and tissue samples are collected at various time points for biomarker analysis, including thymidine kinase activity and circulating tumor DNA. The study seeks to understand primary resistance to these therapies by analyzing the collected samples over the course of treatment and disease progression.

Who should consider this trial

Good fit: Ideal candidates are women aged 18 and older with ER-positive and HER2-negative metastatic breast cancer who have not received prior systemic therapy for their condition.

Not a fit: Patients with prior systemic therapy for metastatic breast cancer or those with HER2-positive disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help identify biomarkers that predict resistance to CDK4/6 inhibitors, leading to more personalized treatment strategies for patients with metastatic breast cancer.

How similar studies have performed: Other studies have explored biomarkers in breast cancer treatment, but this specific approach to identifying resistance to CDK4/6 inhibitors is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Women aged 18 years or older, with a diagnosis of metastatic breast cancer
2. ER-positive and HER2-negative disease as assessed locally either on primary tumor tissue or on a biopsy of a metastasis
3. The patient has not received any prior systemic therapy for metastatic breast cancer (may have received prior hormonal therapy or chemotherapy in the neo/adjuvant setting)
4. The patient is candidate to receive first-line therapy with an aromatase inhibitor (AI) and a CDK4/6 inhibitor per local clinical practice
5. The patient must have evaluable disease according to RECIST 1.1 (either measurable or non-measurable).

   Note: Patients with bone-only disease will be allowed in a specific sub-cohort, which will comprise 10% of the total sample size.
6. Hystologic material from one formalin-fixed, paraffin-embedded (FFPE) tumor block from a diagnostic core or excisional biopsy of a metastatic lesion, taken before study entry must be provided (patients with bone-only disease will be accepted into the trial without a biopsy of the metastatic site). Hystologic material from an additional biopsy (core or excisional) taken at time of disease progression on the study treatment must also be provided, if clinically feasible. When available, hystologic material from an FFPE tumor block from the primary breast cancer must also be submitted.
7. The patient agrees to provide blood samples. at the trial specified time points

Exclusion Criteria:

1. Patients with metastatic disease isolated to the central nervous system (CNS) without metastatic involvement of any other site, unless surgical excision of CNS metastasis has been performed and the tumor tissue is available for the study.
2. Previous or current non-breast malignancies within the last 5 years, with the exception of in situ carcinoma of the cervix and/or adequately treated basal cell or squamous cell carcinoma of the skin

Where this trial is running

Prato, Tuscany

• Hospital Santo Stefano — Prato, Tuscany, Italy (RECRUITING)

Study contacts

• Principal investigator: Luca Malorni — Azienda USL Toscana Centro - Prato
• Study coordinator: Luca Malorni

Conditions: Metastatic Breast Cancer, ER Positive Breast Cancer, HER2-negative Breast Cancer, CDK 4/6 inhibitors, Thymidine Kinase, Palbociclib, Abemaciclib, Ribociclib